In general, the polymer, which is used as a transporter for delivering drug into the organism, needs to be biologically synthesized or to be biodegraded. For example, the polymer such as PLGA is degraded into lactic acid and glycolic acid in the organism, so that it does not have a harmful influence on the organism. Therefore, when the drug transporter is made using the biodegradable polymer, a continuous emission effect can be expected with respect to the various drugs. In particular, for a drug that maintains a constant blood level to exhibit its drug effect only when it is administrated at a predetermined time period, when the drug is encapsulated in the drug transporter made of the biodegradable polymer, the drug is continuously emitted as the polymer carrier is degraded. Accordingly, such sustained releases are applied to the various drugs. The carrier having the emission mechanism includes microsphere, nano-particle, micelle and the like.
The nano-particle is a kind of colloidal non-uniform dispersion particles having a large surface area of a size of several nm to hundreds of nm. As a variety of researches on the preparation, close characteristic examination and drug encapsulation of the nano-particles have been performed, a possibility as the drug transporter thereof has been sufficiently proved. When the nano-particles are introduced into the organism, they are transferred through a variety of methods such as injection, oral administration, skin and the like. At this time, the distributions of the drug are different a little. One of them is a drug transporter using the nano-particles that are colloidal dispersion particles.
The polymer micelle is a promising transporter in a drug delivery system. Typically, the block copolymer micelle, which is comprised of amphoteric block copolymers, has been used as a transporter of hydrophobic drugs such as chemotherapeutic agent (Y. Kazizawa and K. Kataoka, Drug. Del. Rev., 54(2), 203-222 (2002)). A single polymer micelle consists of hundreds of block copolymers and has a diameter of 20˜50 nm. The micelle has two circular parts, i.e., a center of the hydrophobic blocks closely packed and a hydrophilic shell part.
A representative example of the chemotherapeutic agent for treating cancer, which has been used up to now, includes doxorubicin or adriamycin, cisplatin, taxol, 5-fluorouracil, which are widely used in a chemical treatment method for treating the cancer. However, even when only a treatable amount of the agent is administrated, a patient feels a severe pain. The reason of the symptom is that the chemotherapeutic agent acts on not only the cancer cells but only the general cells.
In order to solve the problem, when a chemotherapeutic agent is administrated using nano particles, it is specifically transported to the tissue of the cancer cells, in which the cell junction in the inner wall of the blood vessel is relatively loose, and it cannot transmit well the general cells in which the cell junction is dense, because of the size of the specific particles ranging from several nm to hundreds of nm. Accordingly, if the chemotherapeutic agent is administrated using such principle, the non-specificity of the chemotherapeutic agent can be physically overcome.
In the mean time, one of the problems of the drug transporters, which include the chemotherapeutic agent as the drug, is that the chemotherapeutic agent used is not continuously emitted. In other words, in the case of the conventional drug transporters, the chemotherapeutic agent on the surfaces of the carriers is emitted in the form of diffusion at the early stage, so that the emission at the early stage is considerably high. However, as time goes by, the emission is gradually decreased, so that it is difficult to maintain a constant blood level.
In addition, the large amount of the chemotherapeutic agent should be encapsulated in the transporters. The large amount of the chemotherapeutic agent is used, so that the lost ratio is high in the formulation process of the drug transporter using the chemotherapeutic agent or in the other compounding processes. In this regard, it has been already reported that 50% or more of the chemotherapeutic agent in the transporter is lost after preparing the transporters. Therefore, many researchers put their hearts and souls into the efforts for increasing the encapsulating ratio of the chemotherapeutic agent used as the drug.